Hydrogel wound dressing with synergistic healing promoting function as well as preparation method and application of hydrogel wound dressing

Abstract

The invention discloses a hydrogel wound dressing with a synergistic healing promoting function as well as a preparation method and application thereof. The preparation method comprises the following steps: 1, dissolving oxidized methacrylated hyaluronic acid and dopamine in deionized water to obtain a solution A; the preparation method comprises the following steps: dissolving N-isopropylacrylamide, a photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy) phenyl)-1-acetone and a cross-linking agent N, N '-methylene bisacrylamide in deionized water to obtain a solution B; 2, mixing the solution A and the solution B to obtain a pre-gel solution; or dissolving polyphenylboronic acid ester nanoparticles or polyphenylboronic acid ester-kaempferol with deionized water to obtain a solution C, and mixing the solution C with the solution A and the solution B to obtain a pre-gel solution; and 3, injecting the pre-gel liquid into a mold, and illuminating to obtain the hydrogel wound dressing loaded with the nanoparticles. The hydrogel disclosed by the invention can be used for effectively solving various problems in a wound healing process and promoting rapid and high-quality healing of a wound.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology, specifically relating to a hydrogel wound dressing with synergistic healing function, its preparation method, and its application. Background Technology

[0002] Wound healing is a complex physiological process involving inflammatory response, tissue regeneration and remodeling. It is easily affected by factors such as infection, persistent inflammation, oxidative stress and insufficient wound environment regulation, which can lead to problems such as delayed healing or even healing failure. Clinically, there is an urgent need for wound dressings that have both multi-functional repair capabilities and environmental adaptability.

[0003] Current clinically used wound dressings have significant limitations: First, their antibacterial capabilities are limited, often relying on a single antibacterial component, which easily leads to bacterial resistance and is difficult to address mixed infections. Second, their anti-inflammatory effects are passive, relying solely on physical isolation to reduce external stimuli, unable to actively regulate the release of inflammatory factors to alleviate excessive inflammatory responses, resulting in prolonged inflammation. Third, they lack antioxidant design, failing to remove high concentrations of reactive oxygen species (ROS) in the wound area. ROS accumulation damages granulation tissue, inhibits fibroblast proliferation, and directly hinders the healing process. Fourth, they lack dynamic adaptability to the wound environment; traditional dressings cannot adjust their shape or function according to changes in wound temperature, making it difficult to promote healing "on demand." For example, they cannot actively contract to adhere to the wound surface to reduce exudation and accelerate tissue aggregation.

[0004] Therefore, the development of a hydrogel wound dressing that can synergistically achieve efficient antibacterial, active anti-inflammatory, and precise antioxidant response to reactive oxygen species, and can adapt to the wound environment and accelerate the healing process through temperature-sensitive contraction, is of great significance for solving clinical wound healing problems and improving repair quality, and is also the original intention of this invention. Summary of the Invention

[0005] The technical problem to be solved by this invention is to address the shortcomings of the prior art by providing a hydrogel wound dressing with synergistic healing-promoting function, its preparation method, and its application. This hydrogel can effectively address various problems in the wound healing process, promoting rapid and high-quality wound healing.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a method for preparing a hydrogel wound dressing with synergistic healing-promoting function, characterized by comprising the following steps:

[0007] Step 1: Dissolve methacrylamide-oxidized hyaluronic acid and dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B.

[0008] Step 2: Mix solution A and solution B from step 1 to obtain a pregel solution; or dissolve polyphenylboronic acid nanoparticles or polyphenylboronic acid-kaempferol in deionized water to obtain solution C, and mix solution C with solution A and solution B from step 1 to obtain a pregel solution.

[0009] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it under 365nm light for 30s to 45s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0010] The method for preparing a hydrogel wound dressing with synergistic healing function is characterized in that, in step two, the pregel solution obtained by mixing solution A and solution B contains N-isopropylacrylamide at a concentration of 10–20 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.2–0.6 w / v, N,N'-methylenebisacrylamide at a concentration of 0.003–0.008 w / v, dopamine at a concentration of 0.3–1.2 w / v, and oxymethacrylamide at a concentration of no more than 2 w / v.

[0011] The method for preparing a hydrogel wound dressing with synergistic healing function is characterized in that, in step two, the pregel solution obtained by mixing liquid C with liquid A and liquid B contains N-isopropylacrylamide at a concentration of 10-20 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.2-0.6 w / v, N,N'-methylenebisacrylamide at a concentration of 0.003-0.008 w / v, dopamine at a concentration of 0.3-1.2 w / v, oxymethacrylamide at a concentration of no more than 2 w / v, and polyphenylboronic acid nanoparticles or polyphenylboronic acid-kaempferol at a concentration of no more than 1.2 w / v.

[0012] The method for preparing a hydrogel wound dressing with synergistic healing function is characterized in that the oxidized methacrylamide hyaluronic acid in step one is prepared by methacrylamide oxidation and NaIO4 oxidation of hyaluronic acid.

[0013] The preparation method of the above-mentioned hydrogel wound dressing with synergistic healing function is characterized in that the molecular weight of the hyaluronic acid is 300,000 to 500,000 Da, the mass ratio of methacrylic acid to hyaluronic acid is (2.6 to 5):1, and the molar ratio of NaIO4 to aldehyde groups in hyaluronic acid is (0.4 to 0.8):1.

[0014] The preparation method of the above-mentioned hydrogel wound dressing with synergistic healing function is characterized in that the preparation method of oxidized methacrylamide hyaluronic acid includes the following steps:

[0015] Step 101: Dissolve hyaluronic acid in a mixed solution of N,N-dimethylformamide and deionized water. Under light-protected conditions at 4°C, slowly add methacrylic acid dropwise and react for 6 hours. Under light-protected conditions at 4°C, adjust the pH of the reaction solution to 8-9 with NaOH and continue the reaction for another 6 hours. Then, add 1-5 times the volume of pre-cooled anhydrous ethanol to the reaction system to precipitate the product. Remove the supernatant and centrifuge the precipitate to obtain crude HAMA product. The volume ratio of N,N-dimethylformamide to deionized water is (0.3-1):1.

[0016] Step 102: Dissolve the crude HAMA product obtained in step 101 in deionized water, dialyze it at 4°C in the dark, collect the dialyzed aqueous solution, freeze-dry it to obtain a solid HAMA sample.

[0017] Step 103: Dissolve the HAMA solid sample obtained in step 102 in deionized water to obtain a HAMA solution. Dissolve NaIO4 in deionized water to obtain a NaIO4 solution. Slowly add the NaIO4 solution dropwise to the HAMA solution and react at room temperature in the dark for 1-6 hours. Then add ethylene glycol to quench the unreacted NaIO4 and continue stirring for 1 hour to obtain an OHAMA aqueous solution. Dialyze in the dark and freeze-dry to obtain oxymethacrylamide hyaluronic acid OHAMA.

[0018] The method for preparing a hydrogel wound dressing with synergistic healing function is characterized in that the polyphenylboronic acid ester-kaempferol in step two is prepared by solvothermal polymerization and by loading kaempferol with hydrophobic interaction.

[0019] The above-mentioned hydrogel wound dressing with synergistic healing function is characterized in that the preparation method of the polyphenylboronic acid ester-kaempferol includes the following steps:

[0020] Step 201: Tannic acid, 1,4-phenylenediboric acid, and surfactant F127 are dispersed in a mixed solution of N,N-dimethylformamide and deionized water at a mass ratio of (1-2):(1-2):1. The solution is then transferred to a reactor at 100°C and polymerized for 18-36 hours to obtain an NPs colloidal solution; the volume ratio of N,N-dimethylformamide to deionized water is (3-9):1.

[0021] Step 202: Centrifuge the NPs colloidal solution obtained in step 201, wash with ethanol, and vacuum dry at room temperature to obtain NPs;

[0022] Step 203: Dissolve kaempferol and the NPs obtained in step 202 in N,N-dimethylformamide. Under vigorous stirring, slowly add deionized water. Dialyze the mixture over deionized water for 48 hours to obtain polyphenylboronic acid ester-kaempferol Kae@NPs. The mass ratio of NPs to kaempferol is (1-4):1.

[0023] Furthermore, the present invention also provides a hydrogel wound dressing prepared by the above method.

[0024] Furthermore, the present invention provides an application of the above-mentioned hydrogel wound dressing in the preparation of medical antibacterial repair materials.

[0025] Compared with the prior art, the present invention has the following advantages:

[0026] 1. The hydrogel of this invention integrates antibacterial, anti-inflammatory, and antioxidant functions, with each function working synergistically. Kae@NPs is prepared based on reactive oxygen species (ROS) responsive phenylboronic acid ester bonds. Phenylboronic acid esters can react with ROS at low concentrations. Under the action of ROS, they are oxidized to boric acid, which is then hydrolyzed into phenol and boric acid. The chemical bonds break, releasing Kae, which works synergistically with DA in the hydrogel to achieve ROS scavenging. At the same time, it regulates the M1 / M2 phenotype level of macrophages to achieve anti-inflammatory effects, enabling precise regulation of the wound microenvironment, effectively inhibiting bacterial growth, reducing inflammatory response, and scavenging reactive oxygen species, thus creating a favorable environment for wound healing.

[0027] 2. This invention introduces the thermosensitive polymer PNI to endow the hydrogel with thermosensitive shrinkage function. When the temperature is higher than the critical dissolution temperature, the isopropyl groups change from hydrophilic to hydrophobic, forming intramolecular hydrogen bonds within the polymer chain, leading to a sol-gel transition and automatic shrinkage. This allows it to respond to changes in the local temperature of the wound. When wound infection or inflammation causes an increase in local temperature, the hydrogel shrinks, promoting the convergence of wound edges, reducing the wound area, and accelerating the wound healing process.

[0028] 3. Most of the hydrogel components of this invention are made of biocompatible materials. OHAMA and PNI themselves have excellent biocompatibility, low immunogenicity and degradable metabolism. In biomedical applications, they reduce the body's rejection reaction, promote cell adhesion, proliferation and migration, and promote wound healing.

[0029] 4. The preparation method of the present invention is simple to operate, easy to control, does not require complex equipment and processes, is suitable for large-scale production, and has good application prospects.

[0030] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0031] Figure 1 The Fourier transform infrared spectrum of OHAMA prepared in Example 1 of this invention is shown.

[0032] Figure 2 The Fourier transform infrared spectrum of the Kae@NPs prepared in Example 4 of this invention is shown.

[0033] Figure 3 The images shown are scanning electron microscope (SEM) images of the hydrogels prepared in Comparative Example 1 and Examples 7, 10, and 13 of this invention, with red arrows indicating particles in the gel.

[0034] Figure 4 This is a diagram showing the thermosensitive self-shrinkage results of the hydrogel prepared in Example 13 of the present invention.

[0035] Figure 5 The images show the antibacterial results of hydrogel plate coating prepared in Comparative Example 1 and Examples 7, 10 and 13 of this invention.

[0036] Figure 6 The image shows the antioxidant results of the hydrogels prepared in Comparative Example 1 and Examples 7, 10 and 13 of the present invention.

[0037] Figure 7 The graph shows the cytotoxicity results of the hydrogels prepared in Comparative Example 1 and Examples 7, 10 and 13 of the present invention.

[0038] Figure 8 The image shows the qRT-PCR results of the hydrogels prepared in Comparative Example 1 and Examples 7, 10 and 13 of this invention to regulate the M1 / M2 gene expression in macrophages.

[0039] Figure 9 The figures show the results of wound healing promotion by the hydrogels prepared in Comparative Example 1 and Examples 7, 10 and 13 of the present invention. Detailed Implementation

[0040] The present invention will be specifically described below through examples. These examples are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Experimental methods in the examples that do not specify specific conditions are generally performed under conventional conditions and conditions described in the manual, or according to the conditions recommended by the manufacturer; the equipment, materials, reagents, etc. used are commercially available unless otherwise specified.

[0041] Example 1

[0042] The specific methods for preparing oxymethacrylamide hyaluronic acid (OHAMA) include:

[0043] Step 1: At room temperature, dissolve 1g of hyaluronic acid with a molecular weight of 400,000 Da in 60mL of a mixed solution of N,N-dimethylformamide and deionized water, with a volume ratio of N,N-dimethylformamide to deionized water of 0.5:1; under light-protected conditions at 4℃, slowly add 3g of methacrylic acid dropwise and react for 6h; under light-protected conditions at 4℃, adjust the pH of the reaction solution to 8-9 with NaOH and continue the reaction for 6h; add 1-5 times the volume of pre-cooled anhydrous ethanol to precipitate the product; remove the supernatant, centrifuge the precipitate to obtain crude HAMA product;

[0044] Step 2: Dissolve the crude HAMA product obtained in Step 1 in 30 mL of deionized water, dialyze at 4 °C in the dark, collect the dialyzed aqueous solution, freeze-dry for three days to obtain a solid HAMA sample.

[0045] Step 3: Dissolve the HAMA solid sample obtained in Step 2 in deionized water to obtain a HAMA solution, and dissolve NaIO4 in deionized water to obtain a NaIO4 solution. The molar ratio of NaIO4 to the aldehyde group in hyaluronic acid is 0.6:1. Slowly add the NaIO4 solution to the HAMA solution and react at room temperature in the dark for 4 hours. Add ethylene glycol to quench the unreacted NaIO4 and continue stirring for 1 hour to obtain an OHAMA aqueous solution. Dialyze in the dark and freeze-dry to obtain oxymethacrylamide hyaluronic acid (OHAMA).

[0046] The infrared (FTIR) spectra of HA, HAMA, and OHAMA were determined using a Fourier transform infrared (FTIR) spectrometer. The specific procedure was as follows: HA, HAMA, and OHAMA were each mixed with KBr powder at a mass ratio of 1:100, ground, and then measured using a Fourier transform infrared spectrometer. Figure 1 As shown, in the spectra of OHA and OHAMA, 1723 cm⁻¹ -1 A new absorbance peak appeared at 842 cm⁻¹, corresponding to an aldehyde group or a C=O bond. In the OHAMA spectrum, this peak is at 842 cm⁻¹. -1 A new absorbance peak appeared at 1723 cm⁻¹, corresponding to the C=C bond. -1 and 1628cm -1 The strong absorption peak at this point is due to the superposition of the C=O and C=C stretching vibrations of the methacrylic anhydride-modified group, proving the successful modification of OHAMA.

[0047] Example 2

[0048] The specific methods for preparing oxymethacrylamide hyaluronic acid (OHAMA) include:

[0049] Step 1: At room temperature, dissolve 1g of hyaluronic acid with a molecular weight of 500,000 Da in 60mL of a mixed solution of N,N-dimethylformamide and deionized water, with a volume ratio of N,N-dimethylformamide to deionized water of 1:1; under light-protected conditions at 4℃, slowly add 5g of methacrylic acid and continue the reaction for 6h; under light-protected conditions at 4℃, adjust the pH of the reaction solution to 8-9 with NaOH and continue the reaction for 6h; add 1-5 times the volume of pre-cooled anhydrous ethanol to precipitate the product; remove the supernatant, centrifuge the precipitate to obtain crude HAMA product;

[0050] Step 2: Dissolve the crude HAMA product obtained in Step 1 in 30 mL of deionized water, dialyze at 4 °C in the dark, collect the dialyzed aqueous solution, freeze-dry for three days to obtain a solid HAMA sample.

[0051] Step 3: Dissolve the HAMA solid sample obtained in Step 2 in deionized water to obtain a HAMA solution, and dissolve NaIO4 in deionized water to obtain a NaIO4 solution. The molar ratio of NaIO4 to the aldehyde group in hyaluronic acid is 0.8:1. Slowly add the NaIO4 solution to the HAMA solution and react at room temperature in the dark for 6 hours. Add ethylene glycol to quench the unreacted NaIO4 and continue stirring for 1 hour to obtain an OHAMA aqueous solution. Dialyze in the dark and freeze-dry to obtain oxymethacrylamide hyaluronic acid (OHAMA).

[0052] Example 3

[0053] The specific methods for preparing oxymethacrylamide hyaluronic acid (OHAMA) include:

[0054] Step 1: At room temperature, dissolve 1g of hyaluronic acid with a molecular weight of 300,000 Da in 60mL of a mixed solution of N,N-dimethylformamide and deionized water, with a volume ratio of N,N-dimethylformamide to deionized water of 0.3:1; under light-protected conditions at 4℃, slowly add 2.6g of methacrylic acid and continue the reaction for 6h; under light-protected conditions at 4℃, adjust the pH of the reaction solution to 8-9 with NaOH and continue the reaction for 6h; add 1-5 times the volume of pre-cooled anhydrous ethanol to precipitate the product; remove the supernatant, centrifuge the precipitate to obtain crude HAMA product;

[0055] Step 2: Dissolve the crude HAMA product obtained in Step 1 in 30 mL of deionized water, dialyze at 4 °C in the dark, collect the dialyzed aqueous solution, freeze-dry for three days to obtain a solid HAMA sample.

[0056] Step 3: Dissolve the HAMA solid sample obtained in Step 2 in deionized water to obtain a HAMA solution. Dissolve NaIO4 in deionized water to obtain a NaIO4 solution. The molar ratio of NaIO4 to the aldehyde group in hyaluronic acid is 0.4:1. Slowly add the NaIO4 solution to the HAMA solution and react at room temperature in the dark for 1 hour. Add ethylene glycol to quench the unreacted NaIO4 and continue stirring for 1 hour to obtain an OHAMA aqueous solution. Dialyze in the dark and freeze-dry to obtain oxymethacrylamide hyaluronic acid (OHAMA).

[0057] Example 4

[0058] The specific methods for preparing polyphenylboronic acid ester-kaempferol Kae@NPs include:

[0059] Step 1: Disperse 50 mg tannic acid, 100 mg 1,4-phenylenediboronic acid, and 50 mg surfactant F127 in a mixed solution of 10 mL N,N-dimethylformamide and deionized water (N,N-dimethylformamide to deionized water volume ratio 7:1); then transfer the solution to a reactor at 100 °C and polymerize for 20 h to obtain an NPs colloidal solution; centrifuge the NPs colloidal solution at 10,000 rpm, wash three times with ethanol, and dry in a vacuum oven at room temperature to obtain NPs; then dissolve 10 mg NPs and 5 mg kaempferol in 5.0 mL N,N-dimethylformamide, and slowly add 10 mL deionized water dropwise to the solution under vigorous stirring; dialyze the mixture over deionized water for 48 h to obtain polyphenylenediborate-kaempferol Kae@NPs.

[0060] The Fourier transform infrared (FTIR) spectra of NPs and Kae@NPs were determined using a Fourier transform infrared spectrometer. The specific procedure was as follows: NPs and Kae@NPs powders were mixed with KBr powder at a mass ratio of 1:100, ground, and then measured using a Fourier transform infrared spectrometer. Figure 2 As shown, in the FTIR spectra of NPs and Kae@NPs, at 3421.1 cm⁻¹ -1 and 3413.1cm -1 The absorption peak at 3212 corresponds to the phenolic hydroxyl group (-OH), and the peak intensity of Kae@NPs is lower than that of NPs because the total number of hydroxyl groups is reduced after Kae loading. -1 1717 -1 and 1380cm -1 The different absorption peaks are attributed to the stretching vibrations of the aromatic ring (Ph-H), aldehyde group (C=O), and BO group of phenylboronic acid, respectively, indicating the successful synthesis of NPs. In the FTIR spectrum of NPs@kae, the aldehyde group (C=O) peak is at 1660 cm⁻¹. - A redshift occurred at 1 location, and at 1897cm-1 The presence of an overtone absorption peak at this location is attributed to the aldehyde group and aromatic ring properties of the flavonoid core in kaempferol, demonstrating the successful synthesis of NPs and the successful loading of Kae.

[0061] Example 5

[0062] The specific methods for preparing polyphenylboronic acid ester-kaempferol Kae@NPs include:

[0063] 50 mg of tannic acid, 50 mg of 1,4-phenylenediboronic acid, and 50 mg of surfactant F127 were dispersed in 10 mL of a mixed solution of N,N-dimethylformamide and deionized water, with a volume ratio of N,N-dimethylformamide to deionized water of 3:1. The solution was then transferred to a reactor at 100 °C and polymerized for 18 h to obtain a colloidal solution of poly(phenylenediamine) (NPs). The NPs colloidal solution was centrifuged at 10,000 rpm, washed three times with ethanol, and dried in a vacuum oven at room temperature to obtain NPs. 20 mg of NPs and 5 mg of kaempferol were dissolved in 5.0 mL of N,N-dimethylformamide. Under vigorous stirring, 10 mL of deionized water was slowly added dropwise to the solution. The mixture was dialyzed against deionized water for 48 h to obtain poly(phenylenediamine)-kaempferol Kae@NPs.

[0064] Example 6

[0065] The specific methods for preparing polyphenylboronic acid ester-kaempferol Kae@NPs include:

[0066] 100 mg of tannic acid, 50 mg of 1,4-phenylenediboronic acid, and 50 mg of surfactant F127 were dispersed in 10 mL of a mixed solution of N,N-dimethylformamide and deionized water, with a volume ratio of N,N-dimethylformamide to deionized water of 9:1. The solution was then transferred to a reactor at 100 °C and polymerized for 36 h to obtain a colloidal solution of poly(NPs). The colloidal solution of NPs was centrifuged at 10,000 rpm, washed three times with ethanol, and dried in a vacuum oven at room temperature to obtain NPs. 5 mg of NPs and 5 mg of kaempferol were dissolved in 5.0 mL of N,N-dimethylformamide, and 10 mL of deionized water was slowly added dropwise to the solution under vigorous stirring. The mixture was dialyzed against deionized water for 48 h to obtain poly(phenylenediboronic acid)-kaempferol Kae@NPs.

[0067] Example 7

[0068] The preparation method for the hydrogel wound dressing OHAMA-PNI with synergistic healing-promoting function includes the following steps:

[0069] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0070] Step 2: Mix solution A and solution B from step 1 to obtain a pregel solution; the pregel solution contains N-isopropylacrylamide at a concentration of 18 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.4 w / v, N,N'-methylenebisacrylamide at a concentration of 0.005 w / v, dopamine at a concentration of 0.6 w / v, and oxymethacrylamide hyaluronic acid at a concentration of 1.2 w / v.

[0071] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it under 365nm light for 40s to obtain the hydrogel wound dressing OHAMA-PNI loaded with nanoparticles.

[0072] Example 8

[0073] The preparation method for the hydrogel wound dressing OHAMA-PNI with synergistic healing-promoting function includes the following steps:

[0074] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0075] Step 2: Mix solution A and solution B from step 1 to obtain a pregel solution; the pregel solution contains N-isopropylacrylamide at a concentration of 20 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.6 w / v, N,N'-methylenebisacrylamide at a concentration of 0.008 w / v, dopamine at a concentration of 1.2 w / v, and oxymethacrylamide at a concentration of 2 w / v.

[0076] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 45s to obtain the hydrogel wound dressing OHAMA-PNI loaded with nanoparticles.

[0077] Example 9

[0078] The preparation method for the hydrogel wound dressing OHAMA-PNI with synergistic healing-promoting function includes the following steps:

[0079] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0080] Step 2: Mix solution A and solution B from step 1 to obtain a pregel solution; the pregel solution contains N-isopropylacrylamide at a concentration of 10 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.2 w / v, N,N'-methylenebisacrylamide at a concentration of 0.003 w / v, dopamine at a concentration of 0.3 w / v, and oxymethacrylamide hyaluronic acid at a concentration of 0.8 w / v.

[0081] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it under 365nm light for 30s to obtain the hydrogel wound dressing OHAMA-PNI loaded with nanoparticles.

[0082] Example 10

[0083] The preparation of the hydrogel wound dressing OHAMA-PNI / NPs with synergistic healing-promoting function includes the following steps:

[0084] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0085] Step 2: Dissolve the polyphenylene borate nanoparticles in deionized water to obtain solution C. Mix solution C with solutions A and B from step 1 to obtain a pregel solution. The pregel solution contains N-isopropylacrylamide at a concentration of 18 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.4 w / v, N,N'-methylenebisacrylamide at a concentration of 0.005 w / v, dopamine at a concentration of 0.6 w / v, oxymethacrylamide at a concentration of 1.2 w / v, and polyphenylene borate nanoparticles at a concentration of 0.6 w / v.

[0086] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 40s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0087] Example 11

[0088] The preparation of the hydrogel wound dressing OHAMA-PNI / NPs with synergistic healing-promoting function includes the following steps:

[0089] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0090] Step 2: Dissolve the polyphenylene borate nanoparticles in deionized water to obtain solution C. Mix solution C with solutions A and B from step 1 to obtain a pregel solution. The pregel solution contains 20 w / v N-isopropylacrylamide, 0.6 w / v 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 0.008 w / v N,N'-methylenebisacrylamide, 1.2 w / v dopamine, 2 w / v oxymethacrylamide, and 1.2 w / v polyphenylene borate nanoparticles.

[0091] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 45s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0092] Example 12

[0093] The preparation of the hydrogel wound dressing OHAMA-PNI / NPs with synergistic healing-promoting function includes the following steps:

[0094] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0095] Step 2: Dissolve the polyphenylene borate nanoparticles in deionized water to obtain solution C. Mix solution C with solutions A and B from step 1 to obtain a pregel solution. The pregel solution contains 10 w / v N-isopropylacrylamide, 0.2 w / v 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 0.003 w / v N,N'-methylenebisacrylamide, 0.3 w / v dopamine, 0.8 w / v oxymethacrylamide, and 0.3 w / v polyphenylene borate nanoparticles.

[0096] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 30s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0097] Example 13

[0098] The preparation of the hydrogel wound dressing OHAMA-PNI / Kae@NPs with synergistic healing-promoting function includes the following steps:

[0099] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0100] Step 2: Dissolve the polyphenylene borate-kaempferol prepared in Example 4 in deionized water to obtain solution C. Mix solution C with solution A and solution B from Step 1 to obtain a pregel solution. The pregel solution contains 18 w / v N-isopropylacrylamide, 0.4 w / v 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 0.005 w / v N,N'-methylenebisacrylamide, 0.6 w / v dopamine, 1.2 w / v oxymethacrylamide, and 0.6 w / v polyphenylene borate-kaempferol.

[0101] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 40s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0102] Example 14

[0103] The preparation of the hydrogel wound dressing OHAMA-PNI / Kae@NPs with synergistic healing-promoting function includes the following steps:

[0104] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0105] Step 2: Dissolve the polyphenylene borate-kaempferol prepared in Example 4 in deionized water to obtain solution C. Mix solution C with solution A and solution B described in Step 1 to obtain a pregel solution. The pregel solution contains 20 w / v N-isopropylacrylamide, 0.6 w / v 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 0.008 w / v N,N'-methylenebisacrylamide, 1.2 w / v dopamine, 2 w / v oxymethacrylamide, and 1.2 w / v polyphenylene borate-kaempferol.

[0106] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 45s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0107] Example 15

[0108] The preparation of the hydrogel wound dressing OHAMA-PNI / Kae@NPs with synergistic healing-promoting function includes the following steps:

[0109] Step 1: Dissolve the oxidized methacrylamide hyaluronic acid prepared in Example 1 with dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B;

[0110] Step 2: Dissolve the polyphenylene borate-kaempferol prepared in Example 4 in deionized water to obtain solution C. Mix solution C with solution A and solution B described in Step 1 to obtain a pregel solution. The pregel solution contains 10 w / v N-isopropylacrylamide, 0.2 w / v 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, 0.003 w / v N,N'-methylenebisacrylamide, 0.3 w / v dopamine, 0.8 w / v oxymethacrylamide, and 0.3 w / v polyphenylene borate-kaempferol.

[0111] Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it with 365nm light for 30s to obtain a hydrogel wound dressing loaded with nanoparticles.

[0112] Comparative Example 1

[0113] N-Isopropylacrylamide (NIPAM), photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone (i2959), and crosslinking agent N,N'-methylenebisacrylamide (MBA) were dissolved in deionized water, and then dopamine solution was added and mixed evenly to obtain a pregel solution. The concentration of N-isopropylacrylamide in the pregel solution was 18 w / v, the concentration of 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone was 0.4 w / v, the concentration of N,N'-methylenebisacrylamide was 0.005 w / v, and the concentration of dopamine was 0.6 w / v%. The pregel solution was injected into a mold and irradiated under 365 nm light for 40 s to obtain hydrogel PNI.

[0114] The hydrogels prepared in Examples 7, 10, and 13, as well as the hydrogel prepared in Comparative Example 1, were used as subjects to test various properties of the hydrogels, as detailed below:

[0115] Performance characterization of hydrogels

[0116] The hydrogel PNI prepared in Comparative Example 1 and the hydrogel prepared in Example 7 of this invention were compared.

[0117] OHAMA-PNI, the hydrogel OHAMA-PNI / NPs prepared in Example 10, and the hydrogel OHAMA-PNI / Kae@NPs prepared in Example 13 were immersed in liquid nitrogen, removed, brittle, freeze-dried, sputter-coated with gold, and their pore structure was observed under a scanning electron microscope. The results are as follows: Figure 3 As shown, PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs all exhibit a distinct hydrogel porous morphology. After incorporation of NPs or Kae@NPs, nanoparticle structures are visible in the hydrogel pores, confirming the successful synthesis of OHAMA-PNI / NPs and OHAMA-PNI / Kae@NPs.

[0118] Thermosensitive shrinkage properties of hydrogels

[0119] The constant temperature heating stage was heated to 25℃, 33℃, and 37℃ respectively to simulate the temperature of the hydrogel under storage and physiological conditions. The OHAMA-PNI / Kae@NPs prepared in Example 13 were placed on the heating stage, and photographs were taken at 0 min, 5 min, 10 min, 20 min, and 30 min to record the temperature. The area was measured, and the shrinkage rate was calculated. The shrinkage rate formula is: Shrinkage rate (%) = [(Initial area - Final area) / Initial area] × 100%. Figure 4 As shown, under physiological temperature conditions, the shrinkage rate of OHAMA-PNI / Kae@NPs is significantly higher than that at 25℃ and 33℃, with an overall shrinkage rate of up to 35.29%.

[0120] Validation of the antibacterial properties of the hydrogel

[0121] The antibacterial activity of the hydrogel was studied using Gram-negative bacteria *Escherichia coli*, Gram-positive *Staphylococcus aureus*, and methicillin-resistant *Staphylococcus aureus* (MRSA). A bacterial concentration of 1 × 10⁻⁶ was preferred. 7 CFU / mL; the hydrogel PNI prepared in Comparative Example 1, the hydrogel OHAMA-PNI prepared in Example 7 of this invention, the hydrogel OHAMA-PNI / NPs prepared in Example 10, and the hydrogel OHAMA-PNI / Kae@NPs prepared in Example 13 were co-cultured with bacterial suspension for 12 h; the antibacterial ability of the hydrogels was studied using the plate count method, with the bacterial suspension diluted 100,000 times; the volume of bacterial suspension on the plate was 100 μL; the plates were incubated at 37℃ for 18–20 h, and the colony growth was observed and recorded, colony counts were performed, and the inhibition rate was calculated to evaluate the antibacterial activity of the hydrogels. The inhibition rate was calculated using the formula: Inhibition rate (%) = [(number of colonies in the control group - number of colonies in the experimental group) / number of colonies in the control group] × 100%. Figure 5 As shown in Figure a, the number of colonies decreased significantly after co-culturing with the hydrogel; Figure 5 As shown in Figure b, OHAMA-PNI / NPs and OHAMA-PNI / Kae@NPs exhibited significantly higher antibacterial rates against E. coli and S. aureus than PNI and OHAMA-PNI. OHAMA-PNI / Kae@NPs also showed significantly higher antibacterial rates against MRSA than PNI, OHAMA-PNI, and OHAMA-PNI / NPs. This demonstrates that the hydrogels have good antibacterial effects against both Gram-negative and Gram-positive bacteria. Furthermore, OHAMA-PNI / Kae@NPs also exhibits good antibacterial effects against drug-resistant bacteria.

[0122] Antioxidant experiment of hydrogel

[0123] Nitrogen free radical scavenging experiment: 1 mg of DPPH was dissolved in 25 mL of ethanol to prepare a DPPH solution. PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were added to 3 mL of DPPH solution respectively and reacted at room temperature in the dark for 30 min. The full-wavelength scan curve was recorded. The DPPH scavenging rate was calculated by measuring the absorbance at 517 nm. The formula for nitrogen free radical scavenging rate is: Scavenging rate (%) = (Absorbance of DPPH solution before reaction – Absorbance of DPPH solution after reaction) / Absorbance of DPPH solution before reaction × 100%. Figure 6 As shown in Figure a, the color display and the scavenging rate calculation results demonstrate that the hydrogel has nitrogen free radical scavenging function.

[0124] Oxygen free radical scavenging experiment

[0125] 3 mg of PTIO was dissolved in 20 mL of deionized water to prepare a PTIO solution. PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were added to 3 mL of the PTIO solution respectively, and reacted in a 37°C water bath for 2 hours. The full-wavelength scan curves were recorded. The PTIO scavenging rate was calculated by measuring the absorbance at 557 nm. ABTS was obtained by mixing 7.4 mM ABTS solution with 2.6 mM potassium persulfate in the dark for 24 hours. + Dilute it with deionized water to an absorbance of approximately 0.70 ± 0.02, and then add PNI, OHAMA-PNI, OHAMA-PNI / NPs and...

[0126] OHAMA-PNI / Kae@NPs were mixed with ABTS+ solution and reacted for 20 min, with full-wavelength scan curves recorded. The absorbance at 734 nm was calculated to determine the ABTS+ scavenging rate. The formulas for oxygen free radical scavenging rate are: Scavenging rate (%) = (Absorbance of PTIO solution before reaction – Absorbance of PTIO solution after reaction) / Absorbance of PTIO solution before reaction × 100%; Scavenging rate (%) = (Absorbance of ABTS+ solution before reaction – Absorbance of ABTS+ solution after reaction) / Absorbance of ABTS+ solution before reaction × 100%. Figure 6 As shown in Figures b and c, the color display and the scavenging rate calculation results demonstrate that the hydrogel has the function of scavenging oxygen free radicals.

[0127] Hydroxyl radical (·OH) scavenging experiment: Solutions of 2 mM FeSO4, 5 mM H2O2, and 1.5 mM salicylic acid were prepared in PBS. PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were incubated at 37℃ for 30 min, and full-wavelength scan curves were recorded. The ·OH scavenging rate was calculated by measuring the absorbance at 510 nm. The formula for ·OH scavenging rate is: Scavenging rate (%) = (Absorbance of the hydrogel-free solution - Absorbance of the hydrogel-containing solution) / Absorbance of the hydrogel-free solution × 100%. Figure 6 As shown in Figure d, the color display and the calculation results of the removal rate prove that the hydrogel has the function of ·OH removal.

[0128] Cell culture and cell compatibility experiments

[0129] The toxicity of nanoparticles to human skin fibroblasts (HSF) was evaluated using the CCK-8 toxicity test. HSF was distributed at a concentration of 4 × 10⁻⁶ per well. 3 Cells were seeded at a density suitable for 96-well plates, and PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were immersed in the solution respectively.

[0130] Hydrogel extracts were obtained after 24 hours of culture in DMEM / F12 medium (containing 10% bovine fetal serum and 1% penicillin-streptomycin mixture). HSF cells were cultured in the hydrogel extract for 12, 24, and 72 hours. Then, 10 μL of CCK-8 was added, and the cells were incubated at 37°C for 1 hour. The absorbance of the solution at 450 nm was measured and recorded, and cell viability was calculated. Figure 7 As shown in Figure a, the survival rate of HSF in the four hydrogels was above 80% within 72 hours. Live / dead cell detection and morphological analysis were performed using Calcein-AM / PI dye to observe the live / dead cell ratio. HSF was added at a concentration of 1 × 10⁻⁶ cells per well. 4 Cells were seeded at a density suitable for 96-well plates and cultured with extract. At 12, 24, and 72 hours, cells were stained with a 3:1 Calcein-AM to PI solution. After incubation at 37°C for 0.5 hours, images were taken under a fluorescence microscope for recording the staining results. Figure 7 As shown in Figure b, at 12, 24, and 72 hours, all cells grew well and were almost completely viable.

[0131] Regulation of inflammation-related phenotypes at the cellular level

[0132] Macrophages (RAW264.7) are the first immune cells to infiltrate the surface of biomaterials after transplantation, and they are often used to study inflammatory response mechanisms. RAW264.7 cells were cultured at 5 × 10⁶ cells per well. 5Cells were seeded at the specified cell density into 6-well plates. PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were immersed in DMEM (containing 15% bovine fetal serum and 1% penicillin-streptomycin mixture) for 24 h to obtain hydrogel extracts. After cell attachment, cells were cultured in medium containing 500 ng / mL lipopolysaccharide (LPS) for 18 h to induce RAW264.7 polarization towards the inflammatory phenotype (M1). The LPS-containing medium was then discarded, and cells were cultured in the hydrogel extract for another 18 h. Cells were then collected and subjected to real-time quantitative reverse transcription polymerase chain reaction (qPT-PCR) experiments to measure IL-6, iNOS, and Arg. -1 To assess the mRNA levels and regulate the inflammatory function of the hydrogel. Figure 8 As shown, compared with the positive control group, the mRNA expression of inflammatory markers IL-6 and iNOS was significantly reduced after hydrogel induction, while the expression of anti-inflammatory marker Arg was significantly reduced. -1 Increased mRNA expression indicates that OHAMA-PNI / NPs and OHAMA-PNI / Kae@NPs can regulate the inflammatory microenvironment.

[0133] animal models

[0134] A rat model of full-thickness skin defect caused by MRSA infection was established. Two full-thickness skin defect wounds (d = 8 mm) were created on the back of the rats using a skin punch. 20 μL of 10 [unspecified substance] was dripped into each wound. 9 A CFU / mL MRSA bacterial solution was used, and the wound surface was covered with a medical PU waterproof membrane for one day to successfully construct an infected wound model. PNI, OHAMA-PNI, OHAMA-PNI / NPs, and OHAMA-PNI / Kae@NPs were applied to the wound site and changed every two days. Wound healing was recorded by photographing on days 0, 3, 6, 9, and 12, and the wound area was recorded. The relative wound area was calculated using the formula: Relative wound area (%) = Current wound area / Initial wound area × 100%. Figure 9 As shown, compared with the untreated group, the relative wound area of ​​the hydrogel group was significantly reduced, especially the OHAMA-PNI / Kae@NPs group, which showed a significant reduction in relative wound area compared with the PNI, OHAMA-PNI, and OHAMA-PNI / NPs groups. This demonstrates that the hydrogel has the function of promoting wound healing.

[0135] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the present invention. Any simple modifications, alterations, or equivalent structural changes made to the above embodiments based on the technical essence of the invention shall still fall within the protection scope of the present invention.

Claims

1. A method for preparing a hydrogel wound dressing with synergistic healing-promoting function, characterized in that, Includes the following steps: Step 1: Dissolve methacrylamide-oxidized hyaluronic acid and dopamine in deionized water to obtain solution A; dissolve N-isopropylacrylamide, photoinitiator 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone, and crosslinking agent N,N'-methylenebisacrylamide in deionized water to obtain solution B. Step 2: Mix solution A and solution B from step 1 to obtain a pregel solution; or dissolve polyphenylboronic acid nanoparticles or polyphenylboronic acid-kaempferol in deionized water to obtain solution C, and mix solution C with solution A and solution B from step 1 to obtain a pregel solution. Step 3: Inject the pregel liquid described in Step 2 into the mold and irradiate it under 365nm light for 30s to 45s to obtain a hydrogel wound dressing loaded with nanoparticles.

2. The method for preparing a hydrogel wound dressing with synergistic healing-promoting function according to claim 1, characterized in that, In step two, the pregel solution obtained by mixing solutions A and B contains N-isopropylacrylamide at a concentration of 10–20 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.2–0.6 w / v, N,N'-methylenebisacrylamide at a concentration of 0.003–0.008 w / v, dopamine at a concentration of 0.3–1.2 w / v, and oxymethacrylamide hyaluronic acid at a concentration not exceeding 2 w / v.

3. The method for preparing a hydrogel wound dressing with synergistic healing-promoting function according to claim 1, characterized in that, In step two, the pregel solution obtained by mixing solution C with solutions A and B contains N-isopropylacrylamide at a concentration of 10–20 w / v, 2-hydroxy-2-methyl-1-(4-(2-hydroxyethoxy)phenyl)-1-propanone at a concentration of 0.2–0.6 w / v, N,N'-methylenebisacrylamide at a concentration of 0.003–0.008 w / v, dopamine at a concentration of 0.3–1.2 w / v, oxymethacrylamide at a concentration of no more than 2 w / v, and polyphenylboronic acid nanoparticles or polyphenylboronic acid-kaempferol at a concentration of no more than 1.2 w / v.

4. The method for preparing a hydrogel wound dressing with synergistic healing-promoting function according to claim 1, characterized in that, The methacrylated hyaluronic acid mentioned in step one is prepared by acylation of hyaluronic acid with methacrylic acid and oxidation with NaIO4.

5. The method for preparing a hydrogel wound dressing with synergistic healing-promoting function according to claim 4, characterized in that, The hyaluronic acid has a molecular weight of 300,000 to 500,000 Da, the mass ratio of methacrylic acid to hyaluronic acid is (2.6 to 5):1, and the molar ratio of NaIO4 to the aldehyde group in the hyaluronic acid is (0.4 to 0.8):

1.

6. The method for preparing a hydrogel wound dressing with synergistic healing-promoting function according to claim 5, characterized in that, The preparation method of the oxymethylacrylamide hyaluronic acid includes the following steps: Step 101: Dissolve hyaluronic acid in a mixed solution of N,N-dimethylformamide and deionized water. Under light-protected conditions at 4°C, slowly add methacrylic acid dropwise and react for 6 hours. Under light-protected conditions at 4°C, adjust the pH of the reaction solution to 8-9 with NaOH and continue the reaction for another 6 hours. Then, add 1-5 times the volume of pre-cooled anhydrous ethanol to the reaction system to precipitate the product. Remove the supernatant and centrifuge the precipitate to obtain crude HAMA product. The volume ratio of N,N-dimethylformamide to deionized water is (0.3-1):

1. Step 102: Dissolve the crude HAMA product obtained in step 101 in deionized water, dialyze it at 4°C in the dark, collect the dialyzed aqueous solution, freeze-dry it to obtain a solid HAMA sample. Step 103: Dissolve the HAMA solid sample obtained in step 102 in deionized water to obtain a HAMA solution. Dissolve NaIO4 in deionized water to obtain a NaIO4 solution. Slowly add the NaIO4 solution dropwise to the HAMA solution and react at room temperature in the dark for 1-6 hours. Then add ethylene glycol to quench the unreacted NaIO4 and continue stirring for 1 hour to obtain an OHAMA aqueous solution. Dialyze in the dark and freeze-dry to obtain oxymethacrylamide hyaluronic acid OHAMA.

7. The method for preparing a hydrogel wound dressing with synergistic healing function according to claim 1, characterized in that, The polyphenylene borate-kaempferol described in step two is prepared by solvothermal polymerization and hydrophobic loading of kaempferol.

8. A hydrogel wound dressing with synergistic healing-promoting function according to claim 7, characterized in that, The preparation method of the polyphenylboronic acid ester-kaempferol includes the following steps: Step 201: Tannic acid, 1,4-phenylenediboric acid, and surfactant F127 are dispersed in a mixed solution of N,N-dimethylformamide and deionized water at a mass ratio of (1-2):(1-2):

1. The solution is then transferred to a reactor at 100°C and polymerized for 18-36 hours to obtain an NPs colloidal solution; the volume ratio of N,N-dimethylformamide to deionized water is (3-9):

1. Step 202: Centrifuge the NPs colloidal solution obtained in step 201, wash with ethanol, and vacuum dry at room temperature to obtain NPs; Step 203: Dissolve kaempferol and the NPs obtained in step 202 in N,N-dimethylformamide. Under vigorous stirring, slowly add deionized water. Dialyze the mixture over deionized water for 48 hours to obtain polyphenylboronic acid ester-kaempferol Kae@NPs. The mass ratio of NPs to kaempferol is (1-4):

1.

9. A hydrogel wound dressing prepared by any one of claims 1 to 8.

10. The application of the hydrogel wound dressing as described in claim 9 in the preparation of medical antibacterial repair materials.

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